BSR and BHPR guideline for the treatment of systemic sclerosis Christopher P. Denton, Michael Hughes, Nataliya Gak, Josephine Vila, Maya Buch, Kuntal Chakravarty, Kim Fligelstone, Luke L Gompels, Bridget Griffiths, Ariane L. Herrick, Jay Pang, Louise Parker, Anthony Redmond, Jacob van Laar, Louise Warburton, Voon H. Ong
EULAR/EUSTAR recommendations for the treatment of systemic sclerosis I SSc-related digital vasculopathy (RP, digital ulcers) 1. Calcium channel blockers and iloprost for Raynaud s 2. Intravenous prostanoids (in particular iloprost) should be considered for treatment of digital ulcers in SSc 3. Bosentan should be considered in SSc with multiple digital ulcers II SSc-PAH 4. Bosentan should be strongly considered to treat SSc-PAH 5. Sildenafil may be considered to treat SSc-PAH 6. Sitaxentan is withdrawn and should not be used for SSc-PAH 7. Intravenous epoprostenol should be considered for the treatment of severe SSc-PAH III SSc-related skin involvement 8. Methotrexate may be considered for treatment of skin manifestations of early diffuse SSc IV SSc-ILD V SRC 9. Cyclophosphamide should be considered for treatment of SSc-ILD 10. ACE inhibitors should be used in the treatment of SRC 11. Patients on steroids should be carefully monitored for SRC VI SSc-related gastrointestinal disease 12. PPI should be used for the treatment of SSc-related gastro-oesophageal reflux, 13. Prokinetic drugs should be used for the management of SSc-related symptomatic motility disturbances 14. When malabsorption is caused by bacterial overgrowth, antibiotics may be useful in SSc Kowal-Bielecka et al, Ann Rheum Dis 2009;68:620-628
UKSSG Best practice project (2011-14) Best practice documents available on UKSSG page of the Scleroderma-Royal Free website Stand-alone publications are emerging GI published excellent North American feedback Digital vasculopathy in press Lung fibrosis for submission Cardiac in preparation Renal in draft form http://www.sclerodermaroyalfree.org.uk/ukssg.html
BSR and BHPR guideline for the management of systemic sclerosis Work started September 2012 February 2015 - submitted to BSR and first stage of external peer review presented draft April 2015 Target for completion September 2015 Scope and structure of draft guideline A. General approach to SSc management
Time line for development of BSR BHPR Scleroderma Guideline April 2012 invitation to develop BSR BHPR Scleroderma GL September 2012 core group invited October 2012 Conflict of Interest declarations submitted to BSR Preparatory phase March 2013 Initiation teleconference 20-3-13 Expansion and consolidation of the GL working group April 2013 Announcement of initiative at BSR Scleroderma SIG July 2013 Teleconference to finalise strategy Comprehensive literature review Task allocation Text drafting October 2013 - Teleconference to plan face-to-face meeting February 2014 First Face to Face group meeting June 2014 Teleconference to review progress October 2014 Second Face to face meeting Circulation of first draft guideline Guideline writing Reviewer comments addressed Group circulation and revision Collation and harmonisation of scoring for literature reviews January 2015 final draft guideline circulated in group
The Scleroderma guideline. http://www.rheumatology.org.uk/resources/guidelines/ Submitted January 11th 2016 Accepted April 12th 2016 Published May 2016
http://www.rheumatology.org.uk/resources/guidelines/
Scleroderma guideline format Full guideline Executive summary Text Recommendations Figure Table of key studies
Part A: General approach to SSc management Recommendations in management of early systemic sclerosis: Early recognition and diagnosis of dcssc is a priority with referral to a specialist SSc centre (III, C) Patients with early dcssc should be offered an immunosuppressive agent: MTX, MMF or intravenous cyclophosphamide (CYC) (III/C), although the evidence base is weak. Some might later be candidates for autologous haemopoietic stem cell transplant (ASCT). D-penicillamine is not recommended (IIa/C) Autologous haemopoietic stem cell transplant (ASCT) may be considered in some cases particularly where there is risk of severe organ involvement, balancing concerns about treatment toxicity (IIa/C) Skin involvement may be treated with either MTX (II,B) or MMF (III,C). Other options include CYC (III,C), oral steroid therapy (in as low a dose as possible to suppress symptoms, and with close monitoring of renal function; III,C) and possibly rituximab (III,C) Azathioprine or MMF should be considered after CYC to maintain improvement in skin sclerosis and/or lung function (III,C).
Part B. Key therapies and treatment of organ based disease Raynaud s phenomenon (RP) and digital ulcers (DU) Lung fibrosis Pulmonary hypertension Gut disease Renal complications Cardiac disease Skin manifestations Calcinosis in SSc Musculoskeletal manifestations
NHS England policy for DU in SSc* Sildenafil Prostenoids (iloprost) Bosentan access for severe cases Severe refractory disease: persistent or progressive ulceration of one or more digits causing or threatening tissue loss despite optimal treatment with vasodilators including IV prostanoids and oral sildenafil, or Multiple DUs: 3 or more DUs either currently or occurring in the last 12 months despite IV prostanoids and sildenafil. Challenging process (18 months) with reduced access during development compared with previous arrangements (IFR) *First published: January 2015 Prepared by NHS England Specialised Services Clinical Reference Group for Specialised Rheumatology Published by NHS England, in electronic format only.
Recommendation for autologous stem cell transplantation in systemic sclerosis: Current evidence support the use of ASCT in poor prognosis diffuse SSc that does not have severe internal organ manifestations that render the treatment highly toxic (Ib, B) Final consensus 80%. Definitive statements regarding relative safety and efficacy compared with other immunosuppressive strategies and definition of appropriate cases for ASCT will require further data (III,C) Final consensus 90%.
Agreed pathway for UK patients to be evaluated for autologous stem cell transplantation
Recommendation for non-drug interventions in systemic sclerosis: Although there are very few studies the opinion of the group was that non-drug interventions may be helpful in SSc and are generally not detrimental. Specialist experience of SSc cases is likely to make nondrug interventions more effective and these approaches are popular with patients and can be expected to impact positively on the disease. More research is needed in this area (III, D) Final consensus 100%.
Part C. Service organization and delivery within NHS England SSc must be managed within an integrated system of primary, secondary and tertiary level care. In secondary care it is important to have a specialised multi-disciplinary team Care should be delivered as close to a patient s home as possible but include the essential level of SSc expertise. Education, clinical nurse specialist-led clinic for rapid access and availability of telephone helplines form part of a recommended template for high quality care of SSc. Additional support including self-management advice and social support should also be offered through liaison with patient-based organisations such as Raynaud s and Scleroderma Association and Scleroderma Society. Some services that are required are already commissioned within specialist centres including pulmonary hypertension, home parenteral nutrition, hematological stem cell transplantation and dialysis services for renal failure. These provide a template for delivery of care but it is important that specialist centres are familiar with the particular challenged posed by SSc and its multisystem nature and high burden of complications and co-morbidity.
Conclusions Treatment of scleroderma is improving Established treatments are being used in better ways e.g. immunosuppression Licensed drugs are available for specific complications Access to treatment requires co-ordinated and persistent efforts of medical teams, patients and patient organisations Recent clinical suggest more targeted skin treatments are likely to emerge over the next few years New scleroderma lung fibrosis trials are being planned
Acknowledgements The authors thank the BSR audit and guidelines working group and the BSR office for help, support and encouragement in developing this guideline.